This document discusses renal failure in patients with cirrhosis. It defines hepatorenal syndrome (HRS) as a type of renal failure seen in cirrhosis without intrinsic kidney abnormalities. HRS is classified into types 1-4 depending on severity and timeline of onset. Type 1 has the worst prognosis with median survival of 1-2 weeks. Treatment involves vasoconstrictors like terlipressin combined with albumin for volume expansion. For refractory ascites, large volume paracentesis with albumin is first line, while TIPS may be considered. Renal replacement therapy alone does not improve outcomes in HRS but may be used as a bridge to liver transplantation, which is the definitive treatment for HRS

1. Dr. Nadia Mohsen Abdu Ibrahim
Nephrology Specialist
NMGH

2. Hepatic
patient
with rising
Kidney
function

3. Renal failure in cirrhosis

4. • patients with cirrhosis can develop renal failure for a variety
of reasons besides HRS
• including bacterial infections, shock, the use of nonsteroidal
anti-inflammatory drugs (NSAIDs), and intrinsic renal
diseases.
• The initial management of patients with a rising serum
creatinine level (SCr) depends on the cause. Therefore, the
most important step in treating renal failure in a patient with
cirrhosis is to identify its etiology

5. Assessing kidney function in pts with cirrhosis
Cr assays are subject to interference by
chromogens, bilirubin being the major one
• There is decreased hepatic production of
creatine
• The edematous state that complicates end-
stage liver disease leads to large distribution of
Cr in the body and lower serum Cr
concentration
• Complications such as variceal bleeding,
spontaneous bacterial peritonitis or sepsis lead
to increased Cr tubular excretion
• SCr is a suboptimal marker for renal function
because it may overestimate GFR, mainly on
account of decreased creatinine production or
reduced muscle mass.

6. Definition
renal failure in cirrhosis is established when SCr
increases more than 1.5 mg/dL; this corresponds
to a GFR of approximately 30 mL/minute.
International Ascites Club
AKI in cirrhosis is defined as
an increase in SCr > 50% from the baseline or a rise in SCr
≥ 0.3 mg/dL in <48 hours

8. Causes of renal failure with cirrhosis

9. Causes
(1) HRS, (13%) → 3-month survival probabilities 31%
(2) renal failure associated with infections, (46%)→ 15% survival rate at 3
months
(3) hypovolemia-induced renal failure, (32%) → 46% survival rate
(4) intrinsic renal diseases (9%) → 73% survival rate at 3 months
(5) drug-induced renal failure. (7.5%)
(6) mixed causes (8%),
(7) other causes (2%).

10. Approach to renal failure in cirrhosis
Patients in whom hypovolemia is suspected should receive volume expansion
with albumin (1 g/kg of body weight up to a maximum of 100 g/day).
**Renal failure in the absence of septic shock is currently considered HRS
associated with infections.
Adapted with permission from Lancet.18 Copyright 2003, Elsevier.

11. Hepatorenal Syndrome
HRS is a form of acute or subacute renal
failure characterized by functional renal
vasoconstriction leading to a severe
reduction in GFR without any identifiable
kidney pathology , which develops in
decompensated cirrhosis or ALF
 Functional renal failure
 Absence of Histological changes
 Occurs in patients with chronic liver disease
and progressive liver failure and ascites

12. Pathophysiology
Splanchnic arteriolar vasodilatation
– Decreased effective arterial volume
(EAV)
– Decreased systemic vascular resistance
(SVR)
– Hypotension
– Activation of vasoconstrictor systems
Renin-Angiotensin Angiotensin-
Aldosterone-System
Sympathetic Nervous System
Anti-Diuretic Hormone
Hyperdynamic circulation
• Baroreceptor activation
• SNS activation leading to
1. increased contractility
2. Increased cardiac output

13. Risk Factors
• Advanced ascites (diuretic resistant)
• Large volume paracentesis w/o
albumin (15%)
SBP (20%)
• Infection (SBP)
Prognosis
Worst prognosis of all complications of
cirrhosis
• Type 1 median survival: <2 weeks
• Type 2 median survival: ~6 months

14. Diagnosis of HRS
Diagnosis of exclusion
• Renal failure in cirrhosis:
 Hypovolaemia (GI hemorrhage, shock)
 Nephrotoxins (drugs, contrast)
 Glomerulonephritis (Hep B and C)
 Acute Tubular Necrosis
 Obstruction

15. Diagnostic Criteria
Major Criteria
• Chronic or acute liver disease with advanced
liver failure or portal hypertension (Cirrhosis
with ascites )
• Cr > 1.5mg/dl OR Low GFR < 40mL/min)
• Exclusion of shock, ongoing bacterial infection,
volume depletion, and use of nephrotoxic
drugs
• No improvement in renal function after at
least 2 days with diuretic withdrawal and
volume expansion with albumin. The
recommended dose of albumin is 1 g/kg of
body weight per day up to a maximum of
100 g/day
• Absence of parenchymal kidney disease as
indicated by proteinuria >500 mg/day,
microhematuria (<50 RBC/high power field)
and/or abnormal renal ultrasonography
Arroyo et al; Hepatology 1996; 23: 164-76

16. Diagnostic Criteria
Minor Criteria
• Urine volume < 500mL/day
• Urine sodium < 10mEq/L
• Urine osmolality > plasma osmolality
• Urine RBCs < 50 per hpf
• Serum sodium < 130mEq/L
Arroyo et al; Hepatology 1996; 23: 164-76

17. Classification of the hepatorenal syndrome
Type 1: cirrhosis with rapidly progressive acute renal
failure
Type 2: cirrhosis with subacute renal failure
Type 3: cirrhosis with types 1 or 2 HRS superimposed on
chronic kidney disease or acute renal injury
Type 4: fulminant liver failure with HRS

18. Type 1 hepatorenal syndrome
• The serum creatinine level doubles to greater
than 2.5 mg/dL within 2 weeks
• It is characterized by its rapid progression and
high mortality, with a median survival of only 1
to 2 weeks
• It can be precipitated by spontaneous bacterial
peritonitis and variceal hemorrhage
Munoz S. Medical Clinics of North America July 2008

19. Type 2 hepatorenal syndrome
• Serum creatinine increases slowly and
gradually during several weeks or
months
• Many patients with type 2 HRS
eventually progress to type 1 HRS
because of a precipitating factor
• The median survival of type 2 HRS is
about 6 months
Munoz S. Medical Clinics of North America July 2008

20. Type 3 hepatorenal syndrome
85% of end-stage cirrhotics have intrinsic renal
disease on renal biopsy
Patients with long-standing diabetic nephropathy,
obstructive renal disease, or chronic
glomerulonephritis can develop HRS from a
precipitating event or worsening liver failure
Munoz S. Medical Clinics of North America July 2008

21. Type 4 hepatorenal syndrome
• More than half of patients with ALF
develop HRS,
• The pathophysiology of HRS in ALF is
believed to be similar to that postulated for
HRS occurring in cirrhosis
Munoz S. Medical Clinics of North America July 2008

22. Treatment (Vasopressors)
Midodrine/octreotide (Sandoststin)
• Combination therapy with midodrine (a selective alpha-1
adrenergic agonist) and octreotide (a somatostatin
analog) may be effective and safe
• Midodrine is a systemic vasoconstrictor and octreotide is
an inhibitor of endogenous vasodilator release,
combined therapy would improve renal and systemic
hemodynamics
Terlipressin (Teriss)
• an agonist of the V1 vasopressin receptors (V1Rs) are found in
high density on vascular smooth muscle and cause vasoconstriction by an increase in
intracellular calcium , Cardiac myocytes also possess V1R, has a prolonged
biological half-life compared with other vasopressin
analogues

23. Treatment
• Repeated large volume paracentesis( > 5L) plus albumin
(8 g/L of ascites removed) is the first line of treatment
for refractory ascites
• The use of TIPS (Transjagular intrahepatic
portosysytemic shunt) should be considered in patients
with very frequent requirement of paracentesis or in
those in whom paracentesis is ineffective (e.g. due to the
presence of loculated ascites) → However 5% incidence
to develop de novo AKI post-TIPS.
EASL Guidelines on Ascites, J Hepatol 2010

24. TIPS
• Reduce portal
hypertension
• Increase effective arterial
volume
• Reverse splanchnic
vasodilatation
Complications
• Encephalopathy
• Shunt stenosis
• Haemolysis
• Hyperbilirubinaemia

25. RRT:
• Does not improve outcome in HRS and should be viewed
as a bridge to liver TX in this context
However
AKI in cirrhotic patients is not always secondary to HRS
and may be reversible, Dialysis ttt shouldn’t be withheld
in these circumstances
standard indications apply
• continuous RRT are better tolerated
• Fututre hope: artificial Hepatic assist devices
Liver Transplantation
Treatment of choice for HRS

26. Lastly
• HRS diagnosis by exclusion
• Liver transplantaion is the definitive line of
ttt
Munoz S. Medical Clinics of North America July 2008